This invention relates to a nutritional composition and more particularly to a nutritional composition for the management of protein intake.
Protein intake, especially in human beings, has received the considerable attention of researchers, nutritionists, medical personnel and others concerned with health issues related to alimentation. Indeed, the general awareness of the public of the important links between health, longevity, morbidity and the quality of life in senescence, on the one hand, and diet, on the other hand, is reflected in the popular adage "you are what you eat".
Protein intake is especially relevant in cases where a patient suffers from a malady requiring treatment with one or more therapeutic agents which may be hindered or blocked by the presence of protein. Whether a therapeutic agent will be hindered or blocked and to what extent depends on the nature of the agent and the nature of the malady.
One such malady is Parkinson's disease. Parkinson's disease is an ancient disease and is now understood to be a result of a reduction, sometimes substantial, of levels of an important neurotransmitter, dopamine, as a result of the decadence of nigrostriatal dopaminergic neurons. This results in a variety of manifestations, the most common of which are movement disorders and fatigue. The movement disorders may be uncontrolled actions (including tremor) or poverty of movement such as muscular rigidity.
Until the 1960's, researchers had been attempting to increase levels of dopamine in the brain in order to treat Parkinson's disease. These attempts failed due to the inability of dopamine to cross the blood brain barrier. In the 1960's, the discovery was made that levels of dopamine in the brain could be increased by the oral or parenteral administration of a substance called levodopa. Levodopa is recognized in the literature as a "large neutral amino acid" or "LNAA" (see Nutt, J. G. and Carter, J. H., "Dietary Issues in the Treatment of Parkinson's Disease", Chapter 28 in Therapy of Parkinson's Disease, edited by William C. Koller and George Paulson, (1990) Decker Press, New York) and is a hydroxyphenylalanine of the chemical formula (-)-3-(3,4-dihydroxyphenyl)-L-alanine. As used herein, "LNAA" refers to amino acids which are neutral in that they have only one carboxyl group and one amino group and which generally have a molecular weight greater than 130. Included within the group of LNAAs are phenylalanine, tryptophan, threonine, valine, isoleucine, histidine, leucine, tyrosine and methionine.
It has been known for some time that the reduction of protein intake can assist in the treatment of individuals being administered an LNAA-type therapeutic agent such as levodopa. This is based on the theory that the amino acids constituting protein will compete with the therapeutic agent to cross the blood brain barrier and, thus, will reduce the amount of therapeutic agent ultimately crossing that barrier. This competition results in a lessening of the therapeutic effect of the therapeutic agent or a fluctuation in the response of the patient due to fluctuating levels of competing amino acids in the bloodstream as protein is ingested and metabolized (see Pincus, J. H. et al., Plasma levels of amino acids correlate with motor fluctuations in parkinsonism. Arch. Neurol. (1987) 44:1006-1009; Nutt, J. G., On-off phenomenon: Relation to levodopa pharmacokinetics and pharmacodynamics. Ann. Neurol. (1987) 22:535-540; Leenders, K. L. et al., Inhibition of L-18F-fluordopa uptake into human brain by amino acids demonstrated by positron emission tomography. Ann. Neurol. (1986) 20:258-262).
Protein redistribution diets to date have concentrated on eliminating or reducing total protein in a given meal or meals or for a given period of the day. In the case of Parkinson's disease, some protein redistribution diets have been described as being virtually protein-free until the evening meal (see F. Bracco et al., Protein redistribution diet and antiparkinsonian response to levodopa. Eur. Neurol. (1991) 31:68-71) and as comprising eliminating daytime protein (see Karstaedt, P. J. et al., Standard and controlled-release levodopa/carbidopa in patients with fluctuating Parkinson's disease on a protein redistribution diet. Arch. Neurol. (1991) 48:402-405). Other protein redistribution diets restrict protein consumption during the day to e.g. no more than 7 grams (see Pincus, J. et al., Influence of dietary protein on motor fluctuations in Parkinson's disease. Arch. Neur. (1987) 44:270-272; Pincus, J. et al., Protein redistribution diet restores motor function in patients with dopa-resistent "off" periods. Neurology (1988) 38:481-483; Pincus, J. et al., Plasma levels of amino acids correlate with motor fluctuations in Parkinsonism. Arch. Neurol. (1987) 44:1006-1009).
U.S. Pat. No. 4,690,820 discloses a high-caloric, high-fat dietary composition having a carbohydrate to protein ratio of 3:1 to 3.7:1 also deriving 45-75% of its calories from fat in the amount of 120-325 grams per liter. U.S. Pat. No. 5,206,218 discloses a method and composition for reducing post-prandial fluctuations in LNAA plasma levels wherein the composition administered has a carbohydrate to protein ratio of from about 3:1 to about 6:1, preferably 4:1.
There are a number of disadvantages to the above-noted diets and compositions. A disadvantage to the severely protein-restricted or protein-free diets is that the evening meal must contain a relatively substantial amount of protein in order to satisfy the body's need for essential amino acids and to avoid consequent malnutrition. Compliance with such a regimen can be very difficult for individuals who do not have the appetite or the ability to consume such a substantial amount of protein. Additionally, the often severe onset of parkinsonian symptoms following the high intake of protein in the evening necessary for adequate nutrition is a major disadvantage. Another disadvantage also causing non-compliance is that the protein deficiency borne during the day by the patient may lead to intolerable, or at least bothersome, hunger pangs throughout the day. All of the above diets and compositions suffer from the disadvantage that there is no management of the type of protein (if any) which is administered.
Existing meal replacement products, including low protein products, available on the market tend to rely on high levels of caseinates, such as sodium and calcium caseinates, and/or whey or whey extracts for the source of protein contained in such products. However, these proteins are rich in LNAAs, especially leucine and isoleucine. Accordingly, while a low protein product may be advantageous in that lower protein overall will benefit a patient needing reduced LNAA competition at the blood brain barrier, if the protein which is present in the low protein product is largely constituted by LNAAs, the maximized benefit will not be realized.